The influence of CYP2C19*2 and *17 on on-treatment platelet reactivity and bleeding events in patients undergoing elective coronary stenting
| Autor: | Vera H.M. Deneer, Ankie M. Harmsze, Anthonius de Boer, Christian M. Hackeng, Hendrik J.T. Ruven, Johannes C. Kelder, Jurriën M. ten Berg, Nicoline J. Breet, Jochem W. van Werkum, Olaf H. Klungel, Heleen J. Bouman |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Genotype Platelet Aggregation medicine.medical_treatment Hemorrhage Coronary Artery Disease CYP2C19 Balloon Platelet reactivity Angioplasty Internal medicine Genetics Humans Medicine In patient cardiovascular diseases Myocardial infarction Angioplasty Balloon Coronary General Pharmacology Toxicology and Pharmaceutics Molecular Biology Alleles Genetics (clinical) Polymorphism Genetic business.industry Thrombolysis Platelet Activation medicine.disease Cytochrome P-450 CYP2C19 cardiovascular system Cardiology Molecular Medicine Aryl Hydrocarbon Hydroxylases business TIMI Follow-Up Studies |
| Zdroj: | Pharmacogenetics and Genomics. 22:169-175 |
| ISSN: | 1744-6872 |
| DOI: | 10.1097/fpc.0b013e32834ff6e3 |
| Popis: | To investigate the impact of genotypes on the basis of the loss-of-function variant CYP2C19*2 and the gain-of-function variant CYP2C19*17 on on-treatment platelet reactivity and on the occurrence of Thrombolysis in Myocardial Infarction (TIMI) major bleedings in 820 clopidogrel-treated patients who underwent elective coronary stenting.On-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. Postdischarge TIMI major bleedings within 1 year after enrollment were recorded.In total, 25 major bleedings (3.0% of the study population) were observed. Patients with the CYP2C19*1/*17 and *17/*17 diplotypes exhibited a lower magnitude of platelet reactivity as compared with patients with the CYP2C19*1/*1 diplotype (for the light transmittance aggregometry-adjusted mean difference: -5.8%, 95% confidence interval: -9.6 to -2.1, P=0.002). Patients with the *1/*17 and *17/*17 genotype had a 2.7-fold increased risk in the occurrence of major bleedings [adjusted hazard ratio: 2.7, 95% confidence interval: 1.1-7.0, P=0.039]. The diplotypes *2/*17, *1/*2, and *2/*2 exhibited higher on-treatment platelet reactivity as compared with the wild type (P0.0001). However, this was not translated into an altered risk on major bleedings as compared with the wild type [hazard ratio: 1.3 (0.45-4.0), P=0.60]. Results have not been adjusted for multiple testing.Patients with the CYP2C19*1/*17 and *17/*17 diplotype have a lower magnitude of on-treatment platelet reactivity and are at a 2.7-fold increased risk of postdischarge TIMI major bleeding events after coronary stenting than patients with the *1/*1 genotype. The diplotypes *2/*17, *1/*2, and *2/*2 are associated with increased on-treatment platelet reactivity; however, this is not translated into a lower risk of bleeding events. |
| Databáze: | OpenAIRE |
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